Aberrant parenting and delayed offspring development in rats exposed to lithium

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      Natural lithium (Li) salts, including those used routinely in manic depressive illness, consist of two stable nonradioactive isotopes: lithium-7 (Li-7) (92.6%) and lithium-6 (Li-6) (7.4%). Female rats (3 months old) were treated with either Li-7 chloride or Li-6 chloride or were untreated prior to and during gestation and lactation. Birth weights were lower for Li-treated animals than for normal pups. Maternal behavior of all Li-treated mothers was altered. Li-7 mothers ignored their pups and nursed them infrequently. Li-6 mothers groomed and nursed their pups more often than normal mothers. All pups showed delays in development, especially in the maturation of depth perception. Although Li-6-treated dams were overprotective mothers, their offspring showed longer developmental delays than those of Li-7-treated offspring.
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        • Alexander GJ
        • Lieberman K.W
        • Stokes PE
        Differential lethality of lithium isotopes in mice.
        Biol Psychiatry. 1980; 5: 468-471
        • Alien LD
        • Desai G
        • Tynan MJ
        Prenatal echocardiographic screening for Ebstein's anomaly for mothers on Li therapy.
        Lancet. 1982; ii: 875-876
        • Arnon RG
        • Marin-Garcia J
        • Peeden JN
        Tricuspid valve regurgitation and Li carbonate toxicity in a newborn infant.
        Am J Dis Child. 1981; 135: 941-943
        • Birch NJ
        Metabolic effects of lithium.
        in: Johnson FN Johnson S Lithium in Medical Practice. University Park Press, Baltimore1977: 89-114
        • Bridges RS
        A quantitative analysis of the roles of dosage, sequence, and duration of estradiol and progesterone exposure in the regulation of maternal behavior in the rat.
        Endocrinology. 1984; 114: 930-940
        • Bridges RS
        • Russell DW
        Steroidal interaction in the regulation of maternal behavior in virgin female rats: Effects of testosterone, dihydrotestosterone, estradiol, progesterone and the aromatase inhibitor, l,4,6-androstatriene-3,17-dione.
        J Endocrinol. 1981; 90: 31-40
        • Bridges RS
        • DiBiase R
        • Loundes DD
        • Doherty PC
        Prolactin stimulation of maternal behavior in female rats.
        Science. 1985; 277: 782-784
        • Casparie AF
        • et al.
        Li intoxication during pregnancy.
        Ned Tijdschr Geneeskd. 1974; 118: 1406-1409
        • Cotton FA
        • Wilkinson G
        Advanced Inorganic Chemistry.
        ed 3. Interscience, New York1975
        • Davenport YB
        • Zahn-Wexler C
        • Adland ML
        • Mayfield A
        Early child-rearing practices in families with a manic-depressive parent.
        Am J Psychiatry. 1984; 141: 223-229
        • Duplesses-Tuchman H
        • Mercier-Parot L
        Influence of Li on gestation and prenatal development of the mouse and rat.
        CR Soc Biol (Paris). 1975; 162: 183-186
        • Fieve RR
        The place of lithium in biological psychiatry.
        in: Handbook of Lithium Therapy. University Park Press, Baltimore1980: 3-6
        • Gaensbauer TJ
        • Harmon RJ
        • Cytryn L
        • McKnew DH
        Social and affective development in infants with a manic-depressive parent.
        Am J Psychiatry. 1984; 141: 223-229
        • Harnad HS
        Cardiovascular problems of the newborn and their etiologies.
        Prog Clin Biol Res. 1983; 140: 167-183
        • Hsu JM
        • Rider AA
        Effect of maternal Li ingestion on biochemical and behavioral characteristics of rat pups.
        in: Johnson FM Johnson S Lithium in Medical Practice. University Park Press, Baltimore1978: 279-287
        • Kaplan HI
        • Sadock BJ
        ed 4. Comprehensive Textbook of Psychiatry IV. vol 1. Williams & Wilkins, Baltimore1985
        • Lieberman KW
        • Alexander GJ
        • Stokes P
        Dissimilar effects of Li isotopes on motility in rats.
        Pharmacol Biochem Behav. 1979; 19: 933-935
        • Lieberman KW
        • Stokes PE
        • Kocsis J
        Characteristics of the uptake of Li isotopes into erythrocytes.
        Biol Psychiatry. 1979; 14: 845-849
        • Lieberman KW
        • Chen C
        • Mann J
        In vivo erythrocyte differentiation of naturally occurring isotopic Li abundances.
        in: Fed Proc. 42. 1983: 2110
        • Lieberman KW
        • Sechzer JA
        • Rubino R
        • Alexander GJ
        Li-isotopes: Effects on pregnancy and chronic toxicity in experimental animals.
        in: Fed Proc. 42. 1983: 1362
        • Morrell P
        • Sutherland GR
        • Buamah PK
        • Oo P
        • Bain HH
        Lithium toxicity in a neonate.
        Arch Dis Child. 1983; 58: 539-541
        • Nora JJ
        • Nora AH
        • Toews WH
        Ebstein's anomaly and other congenital heart defects.
        Lancet. 1974; ii: 594-595
        • Rane A
        • Tomson G
        • Bharke B
        Effects of maternal Li therapy in a newborn infant.
        J Pediatr. 1978; 93: 296-297
        • Schou M
        What happened later to Li babies: A follow up study of children without malformations.
        Acta Psychiatr Scand. 1976; 54: 193-197
        • Sechzer JA
        • Faro MD
        • Barker JN
        • Gutierrez S
        • Windle WF
        Developmental behaviors: Delayed appearance in monkeys asphyxiated at birth.
        Science. 1971; 171: 1173-1175
        • Sechzer JA
        • Ervin GN
        • Smith GP
        Loss of visual placing in rats after lateral hypothalamic microinjections of 6-hydroxydopamine.
        Exp Neurol. 1973; 41: 723-732
        • Sechzer JA
        • Lieberman KW
        • Stokes PE
        • Falasco J
        Effects of isotopically pure Li on maternal behavior, development and learning.
        Pharmacologist. 1979; 24: 196
        • Sechzer JA
        • Folstein SE
        • Geiger EH
        • Merivs RF
        • Meehan SM
        The development and maturation of postural reflexes in normal kittens.
        Exp Neurol. 1984; 86: 493-505
        • Sherman WR
        • Munsell LY
        • Wong UH
        Differential uptake of lithium isotopes by rat cerebral cortex and its effects on inositol phosphate metabolism.
        J Neurochem. 1984; 42: 880-882
        • Stokes PE
        • Okamoto M
        • Lieberman KW
        • Alexander G
        • Triana E
        Stable isotopes of Li: In vivo differential distribution between plasma and CSF.
        Biol Psychiatry. 1982; 17: 413-421
        • Von Brendorff I
        • Ertelt W
        Li intoxication in the newborn.
        Monatsschr Kinderheilkd. 1976; 126: 451-453
        • Weinstein MR
        The international register of lithium babies.
        Drug Inform J. 1976; 10: 94-100
        • Weinstein MR
        • Goldfield MD
        Cardiovascular malformations with Li during pregnancy.
        Am J Psychiatry. 1975; 132: 529-531
        • Weissman MM
        • Boyd JH
        Affective disorders: Epidemiology.
        in: ed 4. Comprehensive Textbook of Psychiatry IV. vol I. Williams & Wilkins, Baltimore1985: 764-769
        • Wilson N
        • Forfar JD
        • Godman MJ
        Atrial flutter in the newborn resulting from maternal lithium ingestion.
        Arch Dis Child. 1983; 58: 538-539
        • Zahn-Waxler C
        • Cummings EM
        • McKnew DH
        • Radke-Yarrow M
        Altruism, aggression and social interactions in young children with a manic-depressive parent.
        Child Dev. 1984; 55: 112-122